Package leaflet: Information for the user

Xeredien 20 mg dispersible tablets

Fluoxetine
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Xeredien is and what it is used for
What you need to know before taking Xeredien
How to take Xeredien
Possible side effects
How to store Xeredien
Contents of the pack and other information

1. What Xeredien is and what it is used for

Xeredien 20 mg dispersible tablets contain the active substance fluoxetine, which belongs to a group of
medicines called selective serotonin reuptake inhibitors (SSRIs).
This medicine is used to treat the following conditions:
Adults :

Major depressive episodes
Obsessive-compulsive disorder
Bulimia nervosa: Xeredien is used in combination with psychotherapy to reduce binge eating and purging behaviors

Children and adolescents aged 8 years and older :

Moderate to severe major depressive disorder, when depression does not respond to psychotherapy after 4–6 sessions. Xeredien should be offered to a child or young person with moderate to severe major depressive disorder only in combination with psychotherapy.

How Xeredien works
Each individual has a substance in the brain called serotonin. People who are depressed, or who have
obsessive-compulsive disorder or bulimia nervosa, have lower levels of serotonin than other individuals.
The exact way in which Xeredien and other SSRIs work is not fully understood, but they may help by
increasing the level of serotonin in the brain. Treating these conditions is important to help you feel better.
If left untreated, your condition may persist and may become worse and more difficult to treat.
To ensure that symptoms do not return, treatment may need to continue for several weeks or months.

2. What you need to know before taking Xeredien

Do not take Xeredien if:

You are allergic to fluoxetine or to any of the other ingredients of this medicine (listed in section 6). If you develop a skin rash or other allergic reactions (such as itching, swelling of the lips or face, or shortness of breath), stop taking the tablets immediately and contact your doctor immediately.
You are taking other medicines known as irreversible and non-selective monoamine oxidase inhibitors (MAOIs), as serious or even fatal reactions may occur (e.g. iproniazid used to treat depression). Treatment with Xeredien must not begin until at least 2 weeks after stopping treatment with an irreversible and non-selective MAOI. Do not take any irreversible and non-selective MAOI for at least 5 weeks after stopping Xeredien. If Xeredien has been prescribed for a long period of time and/or at high doses, your doctor should consider a longer interval.
You are taking metoprolol (for the treatment of heart failure), as there is an increased risk that your heart rate may become too slow.

Warnings and precautions
Talk to your doctor or pharmacist before taking Xeredien if any of the following apply to you:
 heart problems;
 onset of fever, muscle stiffness or tremor, changes in mental status such as confusion, irritability, and extreme agitation;
you may be experiencing the so-called "serotonin syndrome" or "neuroleptic malignant syndrome".
Although this syndrome is rare, it may lead to potentially life-threatening conditions; contact your doctor immediately, as it may be necessary to discontinue Xeredien.
 if you have or have previously had episodes of mania; if you experience an episode of mania, contact your doctor immediately, as it may be necessary to discontinue Xeredien;
 history of bleeding disorders or occurrence of bruising or unusual bleeding;
 ongoing treatment with medicines that improve blood fluidity (see 'Other medicines and Xeredien');
 epilepsy or seizures. If you have a seizure (convulsions) or experience an increase in seizure frequency, contact your doctor immediately; it may be necessary to discontinue Xeredien;
 treatment with electroconvulsive therapy (ECT);
 ongoing treatment with tamoxifen (used to treat breast cancer) (see 'Other medicines and Xeredien');
 you begin to feel restless and are unable to sit still or remain still (akathisia). Increasing the dose of Xeredien may worsen this condition;
 diabetes (your doctor may need to adjust your insulin or other antidiabetic treatment dosage);
 liver problems (your doctor may need to adjust your dosage);
 low resting heart rate and/or if you are aware that you may have a deficiency of salts due to severe and prolonged diarrhoea and vomiting (feeling unwell) or due to the use of diuretics (water tablets);
 ongoing treatment with diuretics (water tablets), especially if you are elderly;
 glaucoma (increased pressure inside the eye).
 Medicines such as Xeredien (so-called selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see section 4).
 In some cases, these symptoms may persist after discontinuation of treatment.

Suicidal thoughts and worsening of depression and anxiety disorder.
If you are depressed and/or suffer from anxiety disorders, you may sometimes have thoughts of harming yourself or committing suicide. These thoughts may increase when you first start treatment with antidepressants, as these medicines take time to become effective, usually about 2 weeks but sometimes longer.
You may be more likely to have these thoughts:

If you have previously had thoughts of suicide or self-harm.
If you are a young adult. Clinical trial data have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders who were treated with an antidepressant. If at any time you have thoughts of harming yourself or committing suicide, contact your doctor or go to hospital immediately. You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to inform you if they believe your depression or anxiety is worsening, or if they are concerned about changes in your behaviour.

Children and adolescents aged 8 to 18 years:
When taking this type of medicine, patients under 18 years of age have an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostile behaviour (especially aggressive, oppositional, and angry behaviour). Xeredien should only be used in children and adolescents aged 8 to 18 years for the treatment of moderate to severe major depressive episodes (in combination with psychotherapy) and should not be used to treat other conditions.
Furthermore, in this age group, there is limited information available regarding the long-term safety of Xeredien on growth, puberty, and mental, emotional, and behavioural development.
Nevertheless, and in patients under 18 years of age, the doctor may prescribe Xeredien for the treatment of moderate to severe major depressive episodes in combination with psychotherapy if they consider it the best option for them.
If your doctor has prescribed Xeredien for a patient under 18 years of age and you would like clarification, consult your doctor again. You must inform the doctor if any of the symptoms listed above appear or worsen during treatment with Xeredien in patients under 18 years of age.
Xeredien must not be used in children under 8 years of age.

Other medicines and Xeredien
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Xeredien with:
 some irreversible and non-selective monoamine oxidase inhibitors (MAOIs), some of which are used to treat depression. Irreversible and non-selective MAOIs must not be used with Xeredien, as serious or even fatal reactions (serotonin syndrome) may occur (see 'Do not take Xeredien'). Treatment with Xeredien must begin strictly at least 2 weeks after stopping an irreversible and non-selective MAOI (such as tranylcypromine). Do not take any irreversible and non-selective MAOI for at least 5 weeks after stopping Xeredien.
If Xeredien has been prescribed for a long period and/or at high doses, your doctor may need to consider a longer interval than 5 weeks.
 metoprolol when used for heart failure; there is an increased risk that your heart rate may become too slow.

Xeredien may affect the action of the following medicines (interaction):
 tamoxifen (used to treat breast cancer); since Xeredien may alter blood levels of this medicine, potentially reducing tamoxifen's effectiveness, your doctor may consider prescribing another antidepressant.
 monoamine oxidase inhibitors Type A (MAO-A inhibitors) including moclobemide, linezolid (an antibiotic), and methylene blue chloride (also known as methylene blue, used for acute symptomatic treatment of drug- or chemical-induced methemoglobinemia, for local treatment of skin infections such as plaque psoriasis, acne vulgaris, and cold sores, and as a diagnostic agent for renal function and glomerular filtration rate calculation): due to the risk of serious or even fatal reactions (called serotonin syndrome). Treatment with fluoxetine may be started the day after stopping a reversible MAOI, but your doctor may decide to monitor you closely and use a lower dose of MAO-A inhibitor.
 mequitazine (used for allergic conditions); because taking this medicine with Xeredien may increase the risk of changes in heart electrical activity.
 phenytoin (for epilepsy); since Xeredien may affect blood levels of this medicine, your doctor may need to administer phenytoin more carefully and perform monitoring tests when it is given with Xeredien.
 lithium, selegiline, St. John's wort, tramadol (a painkiller), triptans (for migraine), and tryptophan; when these medicines are taken with Xeredien, there is an increased risk of developing mild serotonin syndrome. Your doctor will perform more frequent checks.
 medicines that may alter heart rhythm, e.g. class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antibacterial agents (e.g. sparfloxacin, moxifloxacin, IV erythromycin, pentamidine), antimalarial treatments, particularly halofantrine, or some antihistamines (astemizole, mizolastine), because taking one or more of these medicines with Xeredien may increase the risk of changes in heart electrical activity.
 anticoagulants (such as warfarin), NSAIDs (non-steroidal anti-inflammatory drugs - such as ibuprofen, diclofenac), aspirin, and other medicines that may improve blood fluidity (including clozapine, used to treat certain mental disorders). Xeredien may alter the effect of these medicines on blood. If treatment with Xeredien is started or stopped while you are taking warfarin, your doctor will need to perform tests, adjust your dosage, and monitor you more frequently.
 cyproheptadine (used for allergic conditions); because it may reduce the effect of Xeredien.
 medicines that lower blood sodium levels (including medicines that increase urine output, desmopressin, carbamazepine, and oxcarbazepine); because these medicines may increase the risk of low blood sodium levels when taken with Xeredien.
 antidepressants such as tricyclic antidepressants, other selective serotonin reuptake inhibitors (SSRIs) or bupropion, mefloquine or chloroquine (used to treat malaria), tramadol (used to treat severe pain), or antipsychotics such as phenothiazines or butyrophenones; because Xeredien may increase the risk of seizures when taken with these medicines.
 flecainide, propafenone, nebivolol, or encainide (for heart conditions), carbamazepine (for epilepsy), atomoxetine, or tricyclic antidepressants (e.g. imipramine, desipramine, and amitriptyline), or risperidone (for schizophrenia), haloperidol, clozapine, alprazolam; because Xeredien may alter blood levels of these medicines, your doctor may need to reduce their dosage when administered with Xeredien.
 diazepam (for anxiety disorders); because Xeredien may prolong the effects of this medicine.

Xeredien with food, drinks, and alcohol
 You may take Xeredien regardless of meals, as preferred.
 You should avoid drinking alcohol while taking this medicine.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Inform your doctor as soon as possible if you are or might be pregnant, or if you are planning a pregnancy.
In newborns whose mothers took fluoxetine during the first months of pregnancy, some studies have reported an increased risk of congenital heart defects. In the general population, about 1 in 100 newborns is born with a heart defect. This figure increases to about 2 in 100 in mothers who took fluoxetine.
When taken during pregnancy, especially during the last three months, medicines like Xeredien may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes the newborn to breathe rapidly and appear bluish. These symptoms usually appear within the first 24 hours after birth.
If this occurs in the newborn, contact your midwife and/or doctor immediately.
It is preferable not to use this treatment during pregnancy unless the potential benefit outweighs the potential risk. Therefore, together with your doctor, you may decide to gradually discontinue Xeredien before or during pregnancy. However, depending on the circumstances, your doctor may recommend that it is better for you to continue taking Xeredien.
Caution is advised when taking this medicine during pregnancy, especially during the late stages of pregnancy or just before delivery, as the following effects have been reported in newborns: irritability, tremor, muscle weakness, persistent crying, difficulty sucking or sleeping.

Breastfeeding
Fluoxetine is excreted in breast milk and may cause adverse effects in newborns. Breastfeeding should only be performed if clearly necessary. If breastfeeding is continued, your doctor may prescribe a lower dose of fluoxetine.

Fertility
In animal studies, fluoxetine has been shown to reduce sperm quality. In theory, this could affect fertility, but no impact on human fertility has been observed so far.

Driving and using machines
Medicines that affect mental function, such as Xeredien, may impair judgment or coordination. Do not drive or operate tools or machinery until you know how Xeredien affects you.

Xeredien contains sorbitol and sodium
The dispersible tablets contain sorbitol: each tablet provides 6.7 mg of sorbitol, equivalent to a maximum of 0.28 mg/kg/day in a 70 kg adult and 0.24 mg/kg/day in a child (see section 3 How to take Xeredien). The presence of sorbitol in dispersible tablets may cause gastrointestinal disturbances and diarrhoea. If your doctor has told you that you have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolize fructose, speak with your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially sodium-free.

3. How to take Xeredien

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Do not take more tablets than prescribed by your doctor.
Swallow the tablets whole with a glass of water, or dissolve them in half a glass of water and
drink the solution immediately and completely. Do not chew the tablets.

Adults:
The recommended dose is:
 Depression: The recommended dose is 1 tablet (20 mg) daily. If necessary, your doctor will review and
adjust the dosage within 3–4 weeks after starting treatment. If required, the dosage may be gradually
increased up to a maximum of 3 tablets (60 mg) daily. The dose should be increased cautiously to ensure
you receive the lowest effective dose.
It is common not to notice an immediate improvement at the beginning of antidepressant treatment. This is
normal, as symptom improvement in depression may only become evident after the first few weeks of therapy.
Patients with depression should be treated for at least 6 months.
 Bulimia nervosa: The recommended dose is 3 tablets (60 mg) daily.
 Obsessive-compulsive disorder: The recommended dose is 1 tablet (20 mg) daily. If necessary, your doctor
will review and adjust the dosage after 2 weeks of treatment. If required, the dosage may be gradually
increased up to a maximum of 3 tablets (60 mg) daily. If no improvement is observed within the first 10 weeks,
your doctor will reassess the treatment.

Use in children and adolescents aged 8 to 18 years with depression:
Treatment must be initiated and supervised by a specialist.
The initial dose is 10 mg daily.
After 1–2 weeks, your doctor may increase the dose to 20 mg daily.
The dose should be increased cautiously to ensure you receive the lowest effective dose. Children with low
body weight may require lower doses. If a satisfactory response to treatment is achieved, your doctor will
reassess the need for continuing treatment beyond 6 months. If no improvement is seen within the first 9 weeks,
your doctor should reconsider the treatment.

Use in elderly patients:
Your doctor will exercise greater caution when increasing the dose, and the daily dosage should generally not
exceed 2 tablets (40 mg). The maximum dose is 3 tablets (60 mg) daily.

Use in patients with liver problems:
If you have a liver disorder or are taking another medicine that could interact with Xeredien, your doctor may
decide to prescribe a lower dose or advise you to take Xeredien on alternate days.

If you take more Xeredien than you should
 If you take too many tablets, go immediately to the nearest hospital emergency department or contact your
doctor without delay.
 If possible, bring the Xeredien packaging with you.
Symptoms of overdose may include: nausea, vomiting, seizures, cardiac disorders (such as irregular heartbeat
and cardiac arrest), respiratory disturbances, and changes in mental state ranging from agitation to coma.

If you forget to take Xeredien
 If you miss a dose, do not worry. Take the next dose at your usual time the following day. Do not take a double
dose to make up for the missed dose.
 Taking the medicine at the same time each day may help you remember to take it regularly.

If you stop taking Xeredien
 Do not stop taking Xeredien without first consulting your doctor, even if you start to feel better. It is important
that you continue taking the medicine as directed.
 Make sure you do not run out of tablets.
When you stop taking Xeredien, you may experience the following symptoms (withdrawal effects): dizziness;
tingling sensations such as pins and needles; sleep disturbances (vivid dreams, nightmares, difficulty falling
asleep); feeling restless or agitated; unusual tiredness or weakness; feelings of anxiety; nausea/vomiting;
tremor; headache.
Most people report that any symptoms occurring upon stopping Xeredien are mild in severity and disappear
within a few weeks. If you experience any symptoms when stopping treatment, contact your doctor.
When you stop taking Xeredien, your doctor will help you gradually reduce the dose over one or two weeks—this
should help reduce the likelihood of withdrawal effects.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
 If at any time you have thoughts of harming yourself or of suicide, contact your doctor or go to hospital
immediately (see section 2).
If you develop a skin rash or an allergic reaction such as itching, swelling of the lips or tongue, difficulty breathing, shortness of breath, stop taking the tablets immediately and inform your doctor immediately.
 If you feel restless and are unable to sit still or remain motionless, you may be experiencing a condition called akathisia; increasing the dose of Xeredien might make you feel worse. If you experience these sensations, contact your doctor.
 Contact your doctor immediately if your skin starts to become red, if you develop a different skin reaction, or if your skin begins to blister or peel. This occurrence is very rare.

The most common side effects (very common side effects which may affect more than 1 in 10 people) are insomnia, headache, diarrhoea, feeling sick (nausea) and tiredness.

Some patients have experienced:
 a group of symptoms (known as “serotonin syndrome”) including unexplained fever with rapid breathing and increased heart rate, sweating, muscle stiffness or tremors, confusion, extreme agitation or drowsiness (rarely only);
 feeling weak, drowsy or confused, particularly in elderly people and in people (elderly) who are taking diuretics (water tablets);
 prolonged and painful erection;
 irritability and extreme agitation;
 heart problems, such as a fast or irregular heartbeat, fainting, collapse or dizziness when standing, which may indicate abnormal heart rhythm.
If you experience any of the side effects listed above, inform your doctor immediately.

The following side effects have also been reported in patients taking Xeredien:

Common (may affect up to 1 in 10 people)
 loss of appetite, weight loss
 nervousness, anxiety
 restlessness, poor concentration
 feeling tense
 reduced sexual desire and sexual problems (including difficulty maintaining an erection during sexual activity)
 sleep problems, unusual dreams, tiredness or drowsiness
 dizziness
 altered taste
 uncontrollable movements
 blurred vision
 sensation of fast or irregular heartbeat
 flushing
 yawning
 digestive problems, vomiting
 dry mouth
 skin rash, hives, itching
 excessive sweating
 joint pain
 increased frequency of urination
 unexplained vaginal bleeding
 feeling unable to stand or chills

Uncommon (may affect up to 1 in 100 people)
 feeling detached from oneself
 strange thoughts
 excessively elevated mood
 orgasm problems
 suicidal thoughts or thoughts of self-harm
 teeth grinding
 muscle contraction, involuntary movements or problems with balance or coordination
 reduced memory
 dilated pupils
 ringing in the ears
 low blood pressure
 shortness of breath
 nosebleeds
 difficulty swallowing
 hair loss
 increased tendency to bruise
 appearance of unexplained bruises or bleeding
 cold sweating
 difficulty passing urine
 sensation of feeling hot or cold
 changes in liver function tests
 gastrointestinal bleeding
 sexual dysfunction
 malaise, feeling strange

Rare (may affect up to 1 in 1,000 people)
 low levels of sodium in the blood
 decrease in blood platelets, increasing the risk of bleeding or bruising
 decrease in white blood cells
 allergic reactions (anaphylactic reactions and serum sickness)
 disturbance in the production of antidiuretic hormone
 unusual, uncontrolled behaviour
 hallucinations
 agitation
 panic attacks
 confusion
 stuttering
 aggression
 seizures, inability to sit still, muscle problems of the mouth and tongue, serotonin syndrome
 heart problems (ventricular arrhythmia including torsade de pointes)
 vasculitis (inflammation of a blood vessel), dilation of blood vessels
 rapid swelling of tissues around the neck, face, mouth and/or throat
 pain in the tube that carries food and water to the stomach
 inflammation of the liver (hepatitis)
 severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome)
 lung problems
 sensitivity to sunlight
 muscle pain
 problems with urination
 milk secretion from the breast, increased prolactin production
 prolonged and painful erection (priapism)
 bleeding from mucous membranes
 changes in levels of certain enzymes in the blood (transaminases, gamma-glutamyl transferase)

Not known
Other side effects occur in a very limited number of people, but their exact frequency is unknown:
 reduction in potassium levels in the blood
 reduction in blood glucose
 chest pain (angina)
 increase in blood pressure

Bone fractures – in patients taking this type of medicine, an increased risk of bone fractures has been observed.

It is likely that most of these side effects will disappear if treatment is continued.

Additional side effects in children and adolescents (8-18 years)
In addition to the possible side effects listed above, Xeredien may slow growth and possibly delay sexual maturation. Suicidal behaviour (suicide attempt and suicidal thoughts), hostile behaviour, mania and nosebleeds have also been commonly reported in children.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xeredien

Keep Xeredien out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging (Exp). The expiry date refers to the last day of that month.
Do not dispose of medicines in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Xeredien contains
The active substance is fluoxetine hydrochloride.
Each tablet contains 20 milligrams (mg) of fluoxetine (as fluoxetine hydrochloride).
The excipients are: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavour, mint flavour, colloidal silica, maize starch, sodium stearyl fumarate and povidone.
Description of the appearance of Xeredien and pack sizes
The tablets are white in colour.
Tablets are available in blisters of 12 and 28 tablets. Not all pack sizes may be marketed.
Marketing Authorisation Holder:
NEOPHARMED GENTILI S.p.A – Via San Giuseppe Cottolengo 15 – 20143 Milan, Italy
Responsible Pharmacist for Batch Release:
Special Product’s Line SPA – Via Fratta Rotonda Vado Largo 1 - 03012 Anagni (FR), Italy
This medicinal product is authorised in the European Economic Area countries under the following names:
Italy: Xeredien